This is the second revision of a RO1 proposal to investigate isocyanate skin and air exposures in an MDI fabric coating factory and implement a field intervention program to reduce isocyanate skin exposures. Reactive isocyanates, widely used as the essential cross-linker for producing polyurethane, have been a leading cause of occupational asthma for over 50 years. Until recently it has been presumed that the respiratory tract is the key route of isocyanate exposure, with clinical practice, research and prevention to-date focused almost exclusively on airborne exposures. There is growing evidence that isocyanate skin exposure can contribute to the development of isocyanate asthma. Despite reduced respiratory isocyanate exposures, isocyanate asthma continues to occur, commonly in work environments where measured airborne levels are below regulatory standards, and also where there is opportunity for skin exposure. This proposed project is a field intervention study aimed at assessing and reducing isocyanate exposures in an MDI polyurethane fabric coating plant employing approximately 100 workers. A recent health survey at this plant showed a high prevalence of sensitization to MDI, with MDI IgG detected in over 1/3 of all workers, despite largely non-detectable MDI air levels. The Specific Aims will be to: Aim 1) Characterize baseline individual worker MDI respiratory and skin exposures using an exposure algorithm based on quantitative air and skin sampling data and biomarkers of exposure Aim 2) Characterize the health status of workers and markers of early disease Aim 3) Design and implement an integrated intervention program to reduce isocyanate skin exposures Aim 4) Evaluate the effectiveness of the intervention program The study will involve an initial quantitative assessment of the worker's respiratory and skin exposures, health status, and selected biomarkers. This will be followed by development and implementation of an integrated intervention program to reduce MDI skin exposures. The effectiveness of the intervention program will be evaluated by comparing work practices, MDI exposures, and relevant biomarkers before and after the intervention. The findings should substantially extend our knowledge concerning isocyanate skin exposure and identify effective strategies to reduce such exposures. The findings should be relevant to the growing number of end-use MDI polyurethane work settings. Public Health Relevance: Isocyanates, widely used chemicals essential to the production of numerous polyurethane foams and other products, remain a leading cause of occupational asthma. Research and controls to-date have focused largely on airborne exposures. Despite reduced air levels exposed workers continue to develop isocyanate asthma. Recent studies suggest that isocyanate skin exposures, which are difficult to monitor and control, may play an important role in the development of isocyanate asthma. This project will be a field intervention study aimed at assessing the extent and health impact of skin exposures to isocyanates in a polyurethane coating factory and also identifying effective strategies to reduce such exposures. The findings should be relevant to the millions of workers who produce and use polyurethane products.